Soluble HLA peptidome: A new resource for cancer biomarkers

Abstract

Using circulating molecular biomarkers to screen for cancer and other debilitating disorders in a high-throughput and low-cost fashion is becoming increasingly attractive in medicine. One major limitation of investigating protein biomarkers in body fluids is that only one-fourth of the entire proteome can be routinely detected in these fluids. In contrast, Human Leukocyte Antigen (HLA) presents peptides from the entire proteome on the cell surface. While peptide-HLA complexes are predominantly membrane-bound, a fraction of HLA molecules is released into body fluids which is referred to as soluble HLAs (sHLAs). As such peptides bound by sHLA molecules represent the entire proteome of their cells/tissues of origin and more importantly, recent advances in mass spectrometry-based technologies have allowed for accurate determination of these peptides. In this perspective, we discuss the current understanding of sHLA-peptide complexes in the context of cancer, and their potential as a novel, relatively untapped repertoire for cancer biomarkers. We also review the currently available tools to detect and quantify these circulating biomarkers, and we discuss the challenges and future perspectives of implementing sHLA biomarkers in a clinical setting.

Comparison of Peptidomes Extracted from Healthy Tissue, Tumour Tissue of the Parotid Glands and Saliva Samples

“…The peptidome -consisting of thousands of peptides: remnants of protein degradation; specific precursor-derived peptides such as hormones, cytokines, or growth factors; and translation products of small open reading frames (smORFs) [16] responds dynamically to changes in the body, providing a rich source of potential biomarkers. This results in the rapid expansion of peptidomics research observed in recent years [17,18], demonstrating characteristic peptidomic patterns of many diseases, including various types of cancer [19][20][21]. Furthermore, it has been shown that peptidomic analyses can detect statistically significant differences observed in bottom-up proteomics [22].…”

IMBAS-MS Discovers Organ-Specific HLA Peptide Patterns in Plasma

“…Beyond clinical applications, another attraction of the sHLA immunopeptidome is that it can serve as an unlimited source of native immunopeptides from diverse HLA backgrounds. As importantly, an extensive repertoire of sHLA peptides from a diversity of healthy donors could potentially serve as a resource to improve the general knowledge about peptide processing and presentability ( 10 , 11 ). In contrast, due to limited analytical sensitivity and tissue accessibility mHLA data is currently restricted to a few hundred different alleles, with on average around 5000 up to 160,000 (HLA-A0201) associated MHC peptides identified by mass spectrometry ( 12 ).…”